Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hattrick in deciphering of heart attack genes

09.02.2009
Scientists of the University of Lübeck, Germany, together with other European and American colleagues, discovered six new genes responsible for the inheritance of heart attacks.

On February 8th, 2009, the online is-sue of the renowned scientific magazine Nature Genetics publishes three large-scale studies in parallel on these findings. The researchers of the European network Cardiogenics, coordinated by the University of Lübeck, are involved in each of the three publications.

The papers follow the success scientists had the year 2007 when they published the very first systematic genome-wide association study for the inheritance of myocardial infarction published in the respected New England Journal of Medicine (Samani et al. 2007). In this work as well as the current studies the complete human genome was scanned for hundreds of thousands genetic markers in thousands of patients. The scientists from Lübeck, Paris, and Boston tested for any single DNA marker, which stands for a tiny section of a chromosome, whether it was accumulated in heart attack patients.

The results add to a still growing list of genes which are responsible for heart attack. The researchers were supported by geneticists an clinicians from Kiel University. Together the two universities operate the biobank popgen. More than 5,000 coronary heart disease patients and healthy individuals from the north German federal state Schleswig-Holstein, who had previously donated blood at popgen, were incorporated into the new study.

New susceptibility locus for coronary artery disease on chromosome 3q22.3
The first of the three publications describes a study by Prof. Dr. Jeanette Erdmann and Prof. Dr. Heribert Schunkert with further colleagues, which was analysed by PD Dr. Inke R. König and Prof. Dr. Andreas Ziegler. In this study, one million genetic markers were evaluated in 1.200 patients with heart attacks (Erdmann et al. 2009). The subsequent replication studies in further 24,000 patients and healthy probands confirmed their initial suspicion: genes causing heart attacks are located on chro-mosomes 3 and 12. One of these genes, the so-called MRAS gene, is thought to play an important role in the biology of blood vessels. The second gene, HNF1A is in close relation to cholesterol metabolism. Both genes offer completely new attempts to understand the underlying pathogenetic mechanisms of heart attack. Ultimately, this knowledge will help to develop new therapies.
Genome wide haplotype association study identifies the SLC22A3-LPAL2 LPA genes cluster as a risk locus for coronary artery disease

The very innovative methodological approach of Dr. David Trégouët from Paris, first author of the second publication in Nature Genetics, looks at the effects of combinations of up to 10 genetic markers that are located in close proximity on the chromosomes (so-called haplotypes) on the risk of acquiring a heart attack (Trégouët et al. 2009). With this approach one can deduce an even higher density of genetic information than for single markers alone. With the increase in information density, the computer capacity necessary for data analysis also rises sharply. However, for the first time Dr. Trégouët employed the European EGEE Grid structure for such genetic analyses. The EGEE-Grid consists of 41,000 main processors (CPUs, central processing units) which provide storage of about five Petabyte (five million gigabyte) in total round-the-clock on hard disk every day. The net carries out 100,000 calculations simultaneously and is financed by the European Union. With this methodology the Cardiogenics consortium identified another region associated with heart attack risk, this time on chromosome 6. The LPA gene which is located in this region regulates the concentration of a certain lipoprotein, a particle which transports fatty acids, such as the lipoprotein (a), in the blood. This knowledge also can be possibly used in future for new therapeutical interventions.

Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants

The hattrick is completed by the work of the Myocardial Infarction Genetics Consor-tium, in which also the Cardiogenics scientists are involved (MIGen Consortium, 2009). With a similar methodical approach like in the first publication another three until now unknown genes associated with heart attack were identified on chromosomes 2, 6 and 21. To support this information and to gain statistical significance, 12,000 patients with heart attack were compared with 12,000 healthy persons. Furthermore this work shows that multiplying each others action the genetic markers in these disease-causing genes together more than double the risk for heart attacks. The higher the number of disease markers is that a patient carries; the higher is the risk to suffer from the disease. This knowledge will help to determine the illness risk in future for early prevention. The aim is therefore to reduce the risk for the arising of a heart attack.

About 750,000 people die of heart attack in Europe every year. The underlying illness of the coronary heart arteries and the heart attack are most frequent causes of death in most Western countries. Hereditary risk factors play a considerable role besides traditional risk factors like age, high blood pressure, fat metabolic disturbances, diabetes mellitus, smoking cigarette and overweight in the emergence of the disease.

The three above mentioned manuscripts add important pieces of the jigsaw to the picture of the inheritance of heart attack. Furthermore the work delivers insights into the emergence and mechanisms of the disease. Some of the findings are rather surprising, because these genes were, until now, not expected to be of any relevance for the development of heart attacks. In future, this knowledge will lead to an improved risk assessment for persons who have not yet fallen ill but who might carry the disease causing genes. Moreover, the findings offer new approaches for pharmacological prevention. From a European point of view it may be of interest that practically all myocardial infarction genes originate from the EU-project Cardiogenics, which is coordinated in Lübeck, Germany (www.cardiogenics.eu) (1-4).

The new results allow a variety of scientific but also medical and clinical conclusions. Firstly, says Prof. Erdmann, the markers identified now offer new attempts to identify persons at risk of obtaining a heart disease. The aim is to concentrate preventative treatment on such people who have the highest risk for heart attacks. Secondly, PD Dr. König points out that this success would not have been possible without the development of novel statistical and information technological methods. Only through these approaches, we are able to find associations in this enormous bulk of data. Thirdly, we now see more clearly just how little we understand about the mechanisms leading to heart attacks, Prof. Schunkert comments on the work. Traditional risk factors, like high blood pressure, diabetes mellitus and increased cholesterol are important for the development of atherosclerosis but there still must be many undiscovered mechanisms that attribute to the disease. Hardly any of the heart attack genes identified thus far fits in the established clichés for the emer-gence of heart attack.

The question, why so many people in our population develop a heart attack, must be reevaluated considering these new findings. It is probable that completely new mechanisms will arise as the emergence of heart disease begins with variants in these newly discovered heart attack genes. However, new mechanisms also mean new approaches in prophylaxis and treatment of heart attacks. It is up to scientists around the world now to elucidate the mechanisms by which these genes cause heart attacks and to explore this knowledge for better prevention and treatment.

References:
1) Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, König IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, Tobin MD, Ziegler A, Thompson JR, Schunkert H; WTCCC and the Cardiogenics Consortium. Genomewide association analysis of coronary artery disease. N Engl J Med. 2007 Aug 2;357(5):443-53.
2) Erdmann J, Großhennig A, Braund PS, König IR, Hengstenberg C, Hall AS, Linsel-Nitschke P, Kathiresan S, Wright B, Trégouët DA, Cambien F, Bruse P, Aherrahrou Z, Wagner AK, Stark K, Schwartz SM, Salomaa V, Elosua R, Melander O, Voight BF, O'Donnell CJ, Peltonen L, Siscovick DS, Altshuler D, Merlini PA, Peyvandi F, Bernardinelli L, Ardissino D, Schillert A, Blankenberg S, Zeller T, Wild P, Schwarz DF, Tiret L, Perret C, Schreiber S, El Mokhtari NE, Schä-fer A, März W, Renner W, Bugert P, Klüter H, Schrezenmeir J, Rubin D, Ball SG, Balmforth AJ, Wichmann HE, Meitinger T, Fischer M, Meisinger C, Baumert J, Peters A, Ouwehand WH, Italian Atherosclerosis, Thrombosis, and Vascular Biology Working Group, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Cardiogenics Consortium, Deloukas P, Thompson JR, Ziegler A, Samani NJ & Schunkert H. New susceptibility locus for coronary artery disease on chromosome 3q22.3. Nature Genetics (in press).
3) Trégouët DA, König IR, Erdmann J, Munteanu A, Braund PS, Hall AS, Großhennig A, Linsel-Nitschke P, Perret C, DeSuremain M, Meitinger T, Wright BJ, Preuss M, Balmforth AJ, Ball SG, Meisinger C, Germain C, Evans A, Arveiler D, Luc G, Ruidavets JB, Morrison C, van der Harst P, Schreiber S, Neureuther K, Schäfer A, Bugert P, El Mokhtari NE, Schrezenmeir J, Stark K, Rubin D, Wichmann HE, Hengstenberg C, Ouwehand WH, Wellcome Trust Case Control Consortium, Cardiogenics Consortium, Ziegler A, Tiret L, Thompson JR, Cambien F, Schunkert H & Samani NJ. Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nature Genetics (in press).

4) MIGen Consortium. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nature Genetics (in press).

Contact:

Prof. Dr. rer. nat. Jeanette Erdmann
(head, Laboratory for Molecular Genetics at the MK II)
Universität zu Lübeck
Medizinische Klinik II
Ratzeburger Allee 160
23538 Lübeck
phone: +49 (0)451 500 4857, +49 (0)174 4744602
e-mail: j.erdmann@cardiogenics.eu
PD Dr. rer. biol. hum. Inke R. König
(vice-director of the Institut für Medizinische Biometrie und Statistik)
Universität zu Lübeck
Institut für Medizinische Biometrie und Statistik
Ratzeburger Allee 160
23538 Lübeck
phone: +49 (0)451 500 6869
e-mail: inke.koenig@imbs.uni-luebeck.de
Prof. Dr. med. Heribert Schunkert
(director of the MK II)
Universität zu Lübeck
Medizinische Klinik II
Ratzeburger Allee 160
23538 Lübeck
phone: +49 (0)451 500 2501
e-mail: heribert.schunkert@uk-sh.de

Rüdiger Labahn | idw
Further information:
http://www.cardiogenics.eu
http://www.uni-luebeck.de

More articles from Studies and Analyses:

nachricht Smart Data Transformation – Surfing the Big Wave
02.12.2016 | Fraunhofer-Institut für Angewandte Informationstechnik FIT

nachricht Climate change could outpace EPA Lake Champlain protections
18.11.2016 | University of Vermont

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>